Zhang et al. (2007) reported a man with onset of a slowly progressive muscular dystrophy from age 11 years. The disorder was characterized by weakness and atrophy of the neck and shoulder girdle muscles with progressive development of ... Zhang et al. (2007) reported a man with onset of a slowly progressive muscular dystrophy from age 11 years. The disorder was characterized by weakness and atrophy of the neck and shoulder girdle muscles with progressive development of limb contractures. There was no apparent cardiac involvement. EMG showed a myopathic pattern, and biopsy showed dystrophic changes. Creatine kinase was mildly elevated. He became wheelchair-bound at age 26 years. The authors reported a second unrelated patient was found incidentally to have an increased serum creatine kinase level at age 47 years. Cardiac work-up showed slight left ventricular basal and septal hypertrophy with mild diastolic dysfunction. There were no neuromuscular symptoms other than intermittent minor weakness of the left arm muscles. Attali et al. (2009) reported an autosomal recessive form of congenital muscular dystrophy, which they described as a myogenic arthrogryposis, in members of a consanguineous Palestinian family. The disorder was characterized by bilateral clubfoot, decreased fetal movements, hypotonia, delayed motor milestones, and progressive motor decline after the first decade. Muscle biopsies in affected individuals revealed variation in size of muscle fibers without necrosis or fibrosis.
In 2 unrelated probands with EDMD4, Zhang et al. (2007) identified 2 different heterozygous mutations in the SYNE1 gene (R257H; 608441.0008 and E646K; 608441.0010). The patient with the E646K mutation had a very mild phenotype, with asymptomatic increased ... In 2 unrelated probands with EDMD4, Zhang et al. (2007) identified 2 different heterozygous mutations in the SYNE1 gene (R257H; 608441.0008 and E646K; 608441.0010). The patient with the E646K mutation had a very mild phenotype, with asymptomatic increased serum creatine kinase. In an unrelated family, the affected mother was heterozygous for a T89M (608442.0001) mutation in the SYNE2 gene. Her affected son was compound heterozygous for the T89M mutation and a variant (V572L; 608441.0009) in the SYNE1 gene, which was also identified in heterozygosity in the unaffected father, casting some doubt on the pathogenicity of the V572L variant. Zhang et al. (2007) postulated a dominant-negative effect of the SYNE mutations, with the possibility of more severe manifestations in the compound heterozygote. In affected members of a Palestinian family with an autosomal recessive form of congenital muscular dystrophy, Attali et al. (2009) identified homozygosity for a splice site mutation (608441.0011) in the SYNE1 gene. Attali et al. (2009) described the disorder as a myogenic arthrogryposis.